Hanford Tank Farms Waste Certification Flow Loop Test Plan

A future requirement of Hanford Tank Farm operations will involve transfer of wastes from double shell tanks to the Waste Treatment Plant. As the U.S. Department of Energy contractor for Tank Farm Operations, Washington River Protection Solutions anticipates the need to certify that waste transfers comply with contractual requirements. This test plan describes the approach for evaluating several instruments that have potential to detect the onset of flow stratification and critical suspension velocity. The testing will be conducted in an existing pipe loop in Pacific Northwest National Laboratory’s facility that is being modified to accommodate the testing of instruments over a range of simulated waste properties and flow conditions. The testing phases, test matrix and types of simulants needed and the range of testing conditions required to evaluate the instruments are describe

Flower Bats (Glossophaga soricina) and Fruit Bats (Carollia perspicillata) Rely on Spatial Cues over Shapes and Scents When Relocating Food

Natural selection can shape specific cognitive abilities and the extent to which a given species relies on various cues when learning associations between stimuli and rewards. Because the flower bat Glossophaga soricina feeds primarily on nectar, and the locations of nectar-producing flowers remain constant, G. soricina might be predisposed to learn to associate food with locations. Indeed, G. soricina has been observed to rely far more heavily on spatial cues than on shape cues when relocating food, and to learn poorly when shape alone provides a reliable cue to the presence of food.Here we determined whether G. soricina would learn to use scent cues as indicators of the presence of food when such cues were also available. Nectar-producing plants fed upon by G. soricina often produce distinct, intense odors. We therefore expected G. soricina to relocate food sources using scent cues, particularly the flower-produced compound, dimethyl disulfide, which is attractive even to G. soricina with no previous experience of it. We also compared the learning of associations between cues and food sources by G. soricina with that of a related fruit-eating bat, Carollia perspicillata. We found that (1) G. soricina did not learn to associate scent cues, including dimethyl disulfide, with feeding sites when the previously rewarded spatial cues were also available, and (2) both the fruit-eating C. perspicillata and the flower-feeding G. soricina were significantly more reliant on spatial cues than associated sensory cues for relocating food.These findings, taken together with past results, provide evidence of a powerful, experience-independent predilection of both species to rely on spatial cues when attempting to relocate food

High Resolution In Vivo Bioluminescent Imaging for the Study of Bacterial Tumour Targeting

The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as lux. BLI is traditionally used as a 2D modality resulting in images that are limited in their ability to anatomically locate cell populations. Use of 3D diffuse optical tomography can localize the signals but still need to be combined with an anatomical imaging modality like micro-Computed Tomography (μCT) for interpretation

Bostonia: The Boston University Alumni Magazine. Volume 17

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Pulse Jet Mixing Tests With Noncohesive Solids

This report summarizes results from pulse jet mixing (PJM) tests with noncohesive solids in Newtonian liquid conducted during FY 2007 and 2008 to support the design of mixing systems for the Hanford Waste Treatment and Immobilization Plant (WTP). Tests were conducted at three geometric scales using noncohesive simulants. The test data were used to independently develop mixing models that can be used to predict full-scale WTP vessel performance and to rate current WTP mixing system designs against two specific performance requirements. One requirement is to ensure that all solids have been disturbed during the mixing action, which is important to release gas from the solids. The second requirement is to maintain a suspended solids concentration below 20 weight percent at the pump inlet. The models predict the height to which solids will be lifted by the PJM action, and the minimum velocity needed to ensure all solids have been lifted from the floor. From the cloud height estimate we can calculate the concentration of solids at the pump inlet. The velocity needed to lift the solids is slightly more demanding than "disturbing" the solids, and is used as a surrogate for this metric. We applied the models to assess WTP mixing vessel performance with respect to the two perform¬ance requirements. Each mixing vessel was evaluated against these two criteria for two defined waste conditions. One of the wastes was defined by design limits and one was derived from Hanford waste characterization reports. The assessment predicts that three vessel types will satisfy the design criteria for all conditions evaluated. Seven vessel types will not satisfy the performance criteria used for any of the conditions evaluated. The remaining three vessel types provide varying assessments when the different particle characteristics are evaluated. The assessment predicts that three vessel types will satisfy the design criteria for all conditions evaluated. Seven vessel types will not satisfy the performance criteria used for any of the conditions evaluated. The remaining three vessel types provide varying assessments when the different particle characteristics are evaluated. The HLP-022 vessel was also evaluated using 12 m/s pulse jet velocity with 6-in. nozzles, and this design also did not satisfy the criteria for all of the conditions evaluated

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility